The proposed research will attempt to elucidate the biochemical mechanisms underlying growth and atrophy of skeletal muscle. Although primarily interested in the cellular events through which increased work induces muscle growth and disuse causes muscle wasting, we also plan to investigate how other physiological factors influence muscle size, including hormones, food supply, and innervation. This work is an outgrowth of our earlier studies on the regulation of amino acid transport, protein synthesis, and nucleic acid synthesis in muscle. A major objective of future research will be to learn more about the process of protein breakdown in this tissue. Relatively little is known at present about this important process, and we hope to clarify how physiological factors influence proteolysis in muscle. Related studies will also investigate certain aspects of amino acid metabolism in muscle. Recent experiments in this laboratory and others have demonstrated that skeletal muscle may be the major site in the body for degradation of certain amino acids and for the production of others. We hoped to determine the physiological significance of these metabolic pathways and to clarify their relationship to the control of protein synthesis and catabolism in muscle. These investigations will be pursued both in intact animals and in isolated rat muscles incubated or cultured in vitro.